STAT1-mediated interferon signatures are associated with preclinical JAK inhibitor sensitivity in T-ALL

Blood. 2025 Jun 5;145(23):2793-2798. doi: 10.1182/blood.2025028566.

Abstract

We used single-cell genomics to characterize a patient with T-cell acute lymphoblastic leukemia treated in the Children's Oncology Group AALL0434 trial with poor clinical outcome despite favorable genomic features, identifying a STAT1-mediated interferon-related transcriptional signature and inflammatory microenvironment associated with sensitivity to small-molecule JAK inhibition.

MeSH terms

  • Child
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Humans
  • Interferons* / genetics
  • Interferons* / metabolism
  • Janus Kinase Inhibitors* / pharmacology
  • Janus Kinase Inhibitors* / therapeutic use
  • Male
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma* / drug therapy
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma* / genetics
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma* / metabolism
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma* / pathology
  • STAT1 Transcription Factor* / genetics
  • STAT1 Transcription Factor* / metabolism

Substances

  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Janus Kinase Inhibitors
  • Interferons